System and apparatus for securing knee joint with a load for magnetic resonance imaging

ABSTRACT

A system that includes: a force sensor assembly adapted to monitor a load as applied on a subject&#39;s knee joint when the force sensor assembly remains in direct contact with the subject&#39;s lower extremity and the load is monitored from inside a main magnet of an MRI scanner; a mobile unit comprising tracks configured to adjust a position of the force sensor assembly; a stationary base on which the mobile unit and the force sensor assembly are located, the mobile unit translatable solely axially on the stationary base; and a processor coupled to the force sensor assembly and programmed to read information encoding the load being monitored by the force sensor assembly, wherein an MRI scan of the knee joint is initiated only when a pre-determined load has been applied to the subject&#39;s knee joint for a pre-determined period of time.

CROSS REFERENCE TO RELATED APPLICATIONS

This application claims benefit of U.S. provisional Patent Application62/094,374, filed Dec. 19, 2014, which is hereby incorporated byreference in its entirely.

TECHNICAL FIELD

This description generally relates to magnetic resonance imaging (MRI).

BACKGROUND

MRI provides soft-tissue images with superior contrast. Thus, MRI hasbecome a widely-used modality for joint imaging, for example, knee jointimaging.

SUMMARY

In one aspect, some implementations provide a system for securing andloading a knee joint of a subject for reproducible magnetic resonanceimaging (MRI). The system includes: a force sensor assembly adapted tomonitor a load as applied on a subject's knee joint when the forcesensor assembly remains in direct contact with the subject's lowerextremity and the load is monitored from inside a main magnet of an MRIscanner; a mobile unit comprising tracks configured to adjust a positionof the force sensor assembly attached thereto; a stationary base onwhich the mobile unit and the force sensor assembly are located, themobile unit translatable solely axially on the stationary base such thatthe subject's knee, as placed over the stationary base, remains in afixed location axially inside the main magnet of the MRI scanner; and aprocessor coupled to the force sensor assembly and programmed to readinformation encoding the load being measured by the force sensorassembly, wherein an MRI scan of the knee joint is initiated only when apre-determined load has been applied to the subject's knee joint for apre-determined period of time such that the subject's knee joint isreproducibly monitored under the pre-determined load.

Implementations may include one or more of the following features.

The mobile unit may be connected to the stationary base by a threadedrod operable to translate the mobile unit solely axially within themagnet and along the stationary base. The mobile unit may include tracksattachable to the force sensor assembly and operable to adjust ananterior/posterior position or a medial/lateral position of the forcesensor assembly. The tracks may include vertical tracks operable toadjust the anterior/posterior position of the force sensor assembly, andhorizontal tracks operable to adjust the medial/lateral position of theforce sensor assembly. The system may include a ratchet operable toactuate the threaded rod to displace the subject's knee joint such thata load is being applied to the knee joint that result in a force actingacross the subject's foot and ankle. The force sensor assembly mayinclude: a load cell configured to measure the force as experienced bythe subject's foot and ankle; and an orthotic boot configured to supportthe subject's foot and ankle by holding the foot and ankle stationarywhile the force experienced by the foot and ankle is being measured bythe load cell.

The stationary base comprises an opening suitable for mounting a coilassembly. The system may further include: a local coil assemblycomprising a base, an aperture on the base, and coils outside of theaperture, wherein the aperture is sized and shaped to fit a subject'sknee joint, and wherein the base is sized and shaped to mate with theopening on the stationary base. The local coil assembly may beconfigured to receive MRI signals emitted from the subject's knee jointin response to radio frequency (RF) pulses and gradient pulses appliedin synchrony. The local coil assembly may be further configured totransmit at least one of the RF pulses.

The system may further include: a shoulder harness attached to thestationary base and adapted to be wrapped around the subject's shouldersuch that the subject's shoulder motion is restrained when the subject'sknee joint is being scanned.

The system may further include: a waist strap attached to the stationarybase and adapted to be worn around the subject's waist such that thesubject's upper body motions are restrained when the subject's kneejoint is being scanned.

The system may further include an MRI scanner that, in turn, mayinclude: a main magnet configured to generate a volume of magnetic fieldwith field inhomogeneity below a defined threshold, the main magnetincluding a bore area sized to accommodate the stationary base on whichthe subject is placed to have the knee jointed scanned; gradient coilsconfigured to generate gradient pulses that provide perturbations to thevolume of magnetic field such that MRI signals encoding an MRI imageaccording to encoding information from the gradient pulses are emittedfrom the knee joint and are subsequently acquired by a local coilassembly mounted on the stationary base; and a control unit incommunication with the processor and configured to operate: (i) thegradient coils to generate the gradient pulses and (ii) the local coilassembly to acquire MRI signals emitted from the knee joint that encodeMRI image when the pre-determined load has been applied for apre-determined period of time. The MRI scanner may further include aradio-frequency (RF) coil in communication with the control unit andwherein the control unit is further configured to operate the RF coil totransmit RF pulses into the subject's knee joint.

The system may further include: an analysis computer adapted toquantify, solely by analyzing MRI images of the knee joint, at least oneof: a cartilage thickness, a cartilage volume, or a cartilage strain.The analysis computer may be adapted to analyze MRI images of the kneejoint from the same subject but from more than one time points. Theanalysis computer may be adapted to determine a cartilage strain bycomparing a first MRI image from a subject during one MRI scan when theknee joint is unloaded and a second MRI image from the subject duringthe same MRI scan when the knee joint is loaded with the pre-determinedload.

In another aspect, some implementations provide a method for performinga magnetic resonance imaging (MRI) scan. The method includes: placing asubject on a stationary base by: securing a knee joint of a subject intoan aperture of a local coil assembly such that the knee joint isrestrained from motion while the subject rests on a stationary baseduring an MRI scan inside a main magnet of an MRI scanner, the localcoil assembly mated with an opening on the stationary base; andconfiguring a force sensor assembly to monitor a load as being appliedon the subject's knee joint when the force sensor assembly is placedinside the main magnet of the MRI scanner; and applying a pre-determinedload on the subject's knee joint while the subject's knee joint issecured to receive the MRI scan; initiating the MRI scan of the kneejoint only when a pre-determined period of time has elapsed afterapplication of the pre-determined load such that the subject's kneejoint is reproducibly monitored under the pre-determined load.

Implementations may provide one or more of the following features.

Applying the pre-determined load on the subject's knee joint mayinclude: using a ratchet system to displace the subject's knee jointsuch that a load is applied to the knee joint which result in a forceacting across the subject's foot and ankle. The method may furtherinclude: using the force sensor assembly to measure the force asapproximately half the subject's body weight when the subject is placedinside the main magnet for the MRI scan. The method may further includeusing an orthotic boot to support the subject's foot and ankle byholding the foot and ankle stationary while the force experienced by thefoot and ankle is being monitored.

The method may further include sliding the subject on the stationarybase into a main magnet of an MRI scanner such that the subject's kneejoint is placed into a volume of magnetic field generated by the mainmagnet with field inhomogeneity below a defined threshold. The methodmay further include: administering an injection of a contrast agent intothe subject to facilitate delineation of knee joint structures from anMRI image of the subject obtained from the MRI scanner. Initiating theMRI scan may include initiating an imaging sequence to highlight an MRIcharacteristic of the knee joint. The MRI characteristic includes atleast one of: a T2 parameter, a T1 parameter, a T1ρ parameter, ahydrogen density parameter, or a magnetization transfer parameter.

The method may further include analyzing a first MRI image of thesubject obtained at a first time point to determine a quantitativebiomarker parameter. The quantitative biomarker parameter includes atleast one of: a cartilage thickness, a cartilage volume, or a cartilagestrain. Determining a quantitative biomarker parameter may includecomparing MRI images obtained from the same subject in one MRI scan whenthe knee joint is unloaded and MRI images obtained from the same subjectduring the same MRI scan when the knee joint is loaded with thepre-determined load. The method may further include analyzing a secondMRI image of the subject obtained at a second time point to determinethe quantitative biomarker parameter. The method may further includedetermining a rate of change for the quantitative biomarker parameter bycomparing the quantitative biomarker parameter determined at the firsttime point with the quantitative biomarker parameter determined at thesecond time point.

The details of one or more aspects of the subject matter described inthis specification are set forth in the accompanying drawings and thedescription below. Other features, aspects, and advantages of thesubject matter will become apparent from the description, the drawings,and the claims.

BRIEF DESCRIPTION OF THE DRAWINGS

Embodiments will now be described, by way of example only, withreference to the drawings, in which:

FIG. 1 shows an example of a magnetic resonance imaging (MRI) systemwith a solenoid magnet for imaging knee joints.

FIG. 2A illustrates a 3D view of an example of components of a systemfor securing a subject's knee joint for MRI imaging.

FIG. 2B illustrates an example of a subject primed for MRI imaging withknee joint secured in a local coil assembly and ready to be loaded withan axial force.

FIG. 3A illustrates an example of a workflow for a subject to receive anMRI scan of the knee joint with reproducible loading conditions.

FIG. 3B illustrates an example of measured force as a function of timeelapse.

FIG. 3C illustrate an example of workflow for acquiring MRI images ofthe knee joint and subsequent image analysis.

FIG. 4A shows an example of an MRI knee joint image manually segmented.

FIG. 4B shows an example of assessing tibiofemoral position after manualsegmentation of the example of MRI knee joint image according to FIG.4A.

FIG. 4C shows an example of a thickness map of the femoral and tibialarticular cartilages after manual segmentation of the example of MRIknee joint image according to FIG. 4A.

FIG. 5A shows an example of measured cartilage strain within the weightbearing regions at two repeat scans.

FIG. 5B shows an example of measured cartilage strain within the weightbearing regions at two repeat scans.

FIG. 5C illustrates the weight bearing regions on femur and tibia.

FIGS. 6A to 6D illustrate an example of image processing to analyzedeformation of cartilage in the weight bearing region.

FIG. 7 illustrates an example of analyzing 3D T1ρ relaxation-timemapping of the tibial cartilage.

FIG. 8 shows examples of preoperative cartilage deformation under anaxial force of 50% body weight from five subjects.

FIGS. 9A to 9C show example analysis results of cartilage quantitativeMRI values and cartilage thickness before and after the surgery of asubject from FIG. 8.

FIGS. 10A to 10C show example analysis results of cartilage quantitativeMRI values and cartilage thickness before and after the surgery ofanother subject from FIG. 8.

Like reference symbols in the various drawings indicate like elements.

DETAILED DESCRIPTION

An MRI-compatible system is developed for securing a subject's kneejoint and generally maintaining a known mechanical load on the kneejoint. The system is capable of setting and generally maintaining amechanical load on the knee joint of a subject while the subjectreceives an MRI scan inside a main magnet of an MRI scanner. In additionto positioning the subject's knee joint securely with repeatability inpatient-specific knee joint orientation for the MRI scan, the system isalso capable of delivering patient-specific load to the subject's kneesuch that the subject's knee joint can be scanned at different timepoints when the knee joint is under generally the same patient-specificmechanical load. The system may enable longitudinal studies of kneejoints to track cartilage degeneration as well as cartilage response tosurgical intervention and/or drug therapies. Such longitudinal studiesgenerally include subjecting to patient to loading condition overseveral time points. In these longitudinal studies, the MRI scan may beinitiated only after an initial period when the mechanical load on theknee joint has settled. As MRI scans of the knee joints can be performedwith reproducibility when the knee joint is under a load condition,subsequent analysis can quantify features of, for example, cartilagedeformation caused by the load. Such features can be tracked in alongitudinal manner to reveal interesting trend to enable prognosticpredictions.

FIG. 1 shows an example of a magnetic resonance imaging (MRI) system 5with a solenoid magnet for imaging knee joints. The MRI system 5includes a workstation 10 having a display 12 and a keyboard 14. Theworkstation 10 includes a processor 16 that is a commercially availableprogrammable machine running a commercially available operating system.The workstation 10 provides the operator interface that enables scanprescriptions to be entered into the MRI system 5. The workstation 10 iscoupled to four servers including a pulse sequence server 18, a dataacquisition server 20, a data processing server 22, and a data storeserver 23. The work station 10 and each server 18, 20, 22 and 23 areconnected to communicate with each other.

The pulse sequence server 18 functions in response to instructionsdownloaded from the workstation 10 to operate a gradient system 24 andan RF system 26. Gradient waveforms necessary to perform the prescribedscan are produced and applied to the gradient system 24 that excitesgradient coils in an assembly 28 to produce the magnetic field gradientsGx, Gy and Gz used for position encoding MR signals. The gradient coilassembly 28 forms part of a magnet assembly 30 that includes apolarizing magnet 32 and a whole-body RF coil 34.

RF excitation waveforms are applied to the RF coil 34 by the RF system26 to perform the prescribed magnetic resonance pulse sequence.Responsive MR signals detected by the RF coil 34 or a separate localcoil (not shown in FIG. 1) are received by the RF system 26, amplified,demodulated, filtered, and digitized under direction of commandsproduced by the pulse sequence server 18. The RF system 26 includes anRF transmitter for producing a wide variety of RF pulses used in MRpulse sequences. The RF transmitter is responsive to the scanprescription and direction from the pulse sequence server 18 to produceRF pulses of the desired frequency, phase and pulse amplitude waveform.The generated RF pulses may be applied to the whole body RF coil 34 orto one or more local coils or coil arrays (not shown in FIG. 1).

The RF system 26 also includes one or more RF receiver channels. Each RFreceiver channel includes an RF amplifier that amplifies the MR signalreceived by the coil to which it is connected and a detector thatdetects and digitizes the I and Q quadrature components of the receivedMR signal.

The pulse sequence server 18 also optionally receives patient or subjectdata from a physiological acquisition controller 36. The controller 36receives signals from a number of different sensors connected to thepatient, such as ECG signals from electrodes or respiratory signals froma bellows. Such signals are typically used by the pulse sequence server18 to synchronize, or “gate”, the performance of the scan with thesubject's respiration or heart beat.

The pulse sequence server 18 also connects to a scan room interface 38that receives signals from various sensors associated with the conditionof the patient and the magnet system. It is also through the scan roominterface 38 that a patient positioning system 40 receives commands tomove the patient to desired positions during the scan by translating thepatient table 41.

The digitized MR signal samples produced by the RF system 26 arereceived by the data acquisition server 20. The data acquisition server20 operates in response to instructions downloaded from the workstation10 to receive the real-time MR data and provide buffer storage such thatno data is lost by data overrun. In some scans the data acquisitionserver 20 does little more than pass the acquired MR data to the dataprocessor server 22. However, in scans that require information derivedfrom acquired MR data to control the further performance of the scan,the data acquisition server 20 is programmed to produce such informationand convey it to the pulse sequence server 18. For example, duringprescans, MR data is acquired and used to calibrate the pulse sequenceperformed by the pulse sequence server 18. Also, navigator signals maybe acquired during a scan and used to adjust RF or gradient systemoperating parameters or to control the view order in which k-space issampled. In all these examples the data acquisition server 20 acquiresMR data and processes it in real-time to produce information that isused to control the scan.

The data processing server 22 receives MR data from the data acquisitionserver 20 and processes it in accordance with instructions downloadedfrom the workstation 10. Such processing may include, for example,Fourier transformation of raw k-space MR data to produce two or threedimensional images, the application of filters to a reconstructed image,the performance of a back projection image reconstruction of acquired MRdata; the calculation of functional MR images, the calculation of motionor flow images, and the like.

Images reconstructed by the data processing server 22 are conveyed backto the workstation 10 where they are stored. Real-time images are storedin a data base memory cache (not shown) from which they may be output tooperator display 12 or a display 42 that is located near the magnetassembly 30 for use by attending physicians. Batch mode images orselected real time images are stored in a host database on disc storage44. When such images have been reconstructed and transferred to storage,the data processing server 22 notifies the data store server 23 on theworkstation 10. The workstation 10 may be used by an operator to archivethe images, produce films, or send the images via a network to otherfacilities.

As shown in FIG. 1, the RF system 26 may be connected to the whole bodyRF coil 34 while a transmitter section of the RF system 26 may connectto one RF coil and its receiver section may connect to a separate RFreceive coil. Often, the transmitter section is connected to the wholebody RF coil 34 and each receiver section is connected to a separatelocal coil.

FIG. 2A illustrates a 3D view of an example of components of a system200 for securing a subject's knee joint for MRI imaging while FIG. 2Billustrates an example of a subject primed for MRI imaging with kneejoint secured in a local coil assembly and ready to be loaded with anaxial force. System 200 includes a stationary base 202, on which forcesensor assembly is located. Stationary base 202 may be mounted on apatient bed of patient positioning system 40 of MR system 5. Thestationary base be rectangular shaped and may include a void 202H. Thevoid 202H may be sized and shaped to fit the base of a local coilassembly. The stationary base may include aperture 202A on which mobileunit 204 may be attached. In the illustration, aperture 202A ispredominantly an aperture along an axial direction.

In this example, force sensor assembly includes mobile unit 204 and loadcell 206. As illustrated, mobile unit 204 may be connected to thestationary base 202 by a threaded titanium rod 203A to permit only axialtranslation of the mobile unit along the stationary base. Mobile unit204 may include horizontal track 205A and vertical track 205B fastenedthrough lock pin 207. In this illustrated example, horizontal track 205Ais operable to effectuate medial/lateral movement while vertical track205B is operable to implement anterior/posterior adjustment.MRI-compatible load cell 206 may be attached to horizontal track 205Aand vertical track 205B. Together, horizontal track 205A and verticaltrack 205B can adapt to the shape and size of a subject's foot by virtueof medial/lateral and anterior/posterior adjustments to accommodatedifferent subjects. The medial/lateral and anterior/posterior directionsgenerally refer to spatial coordinates inside a bore area of the mainmagnet of an MRI scanner. Horizontal track 205A and vertical track 205Bmay also be adjusted such that forces/torques in other directions may beapplied in the corresponding directions. In this illustration, load cell206 is a 6-degree of freedom load cell. The load cell may measure andquantify the load applied to the subject's knee joint as manifested as aforce on the subject's lower extremity, including the foot and ankle.The load cell may communicate with the computer, sitting outside of thescanning room. In some instances, the communication is wiredcommunication. A computer—with data acquisition software installed—mayrecord, in real time, the load as measured by the load cell.

As illustrated in FIG. 2B, an orthotic boot 208 may be rigidly fastenedto the load cell 206 while the load cell 206 can be mounted on themobile unit 204. In this example, the orthotic boot 208 supports thefoot of the subject by holding stationary during an MRI scan. In someimplementations, a ratchet may be used to actuate the threaded rod 203Ato translate the mobile unit 204 axially. This axial translation candisplace the knee joint already secured on the stationary base 202,resulting in a load that acts across the lower extremity of the subject.In other implementations, a pushing force may be automatically appliedtowards the knee joint and from the orthotic boot region after the kneejoint of the subject has been secured for imaging. In theseimplementations, the pushing force may be monitored, for example, by aforce sensor such as load cell 206 so that the loading condition of theknee joint may be quantified as a feedback and adjustments of thepushing force may be performed.

In the illustration of FIG. 2B, a stabilization mechanism generallyrestrains the upper body motions of the subject. For example, a shoulderharness and a waist strap can be used to tie down the subject's upperbody to restrict its motion. In some instances, additional straps andpadding can be used to secure the knee in the coil and the leg to thestationary base.

FIG. 3A illustrates an example of a workflow 300 for a subject toreceive an MRI scan of the knee joint with reproducible load conditions.In a typical hospital setting, patients may arrive for receiving MRIscans so that their knee joints can be monitored at various longitudinaltime points. In particular, implementations disclosed herein allow MRIscans to be performed on the same subject's knee joint with reproducibleload conditions. The manner in which MRI scans are reliably generated atvarious time points with reproducible and consistent load conditionsallows longitudinal monitoring of a subject's knee joint. Suchlongitudinal monitoring may enable intra-patient tracking of theprogression of cartilage pathology, or response to a surgery/drug. Somelongitudinal studies may quantify cartilage change in thickness, contactarea, meniscal extrusion and T1ρ and/or T2 outcomes. Quantification ofsuch biomarker parameters over various time points may provideprognostic value by rendering predictions of the long-term response ofthe tissue of the knee joint to injury or response to surgery. In someinstance, MRI scans and subsequent quantification of biomarkerparameters can be performed pre-operatively and then as at various timepoints post-operatively. The rate of change of a quantified biomarkerparameter as a function of time after surgery can be used to indicatelikelihood of developing tissue degeneration even after surgery. Inother instances, such MRI scans and subsequent quantification ofbiomarker parameters may be performed longitudinally to monitor thesubject's knee joint before the administration of a therapeutic drug andthen track the response of the subject after the administrations of thetherapeutic drug. In a similar manner, a quantified biomarker parametercan be extrapolated after initiation of a therapeutic intervention (suchas a drug or physical therapy). For example, the rate of change of thequantified biomarker parameter can be used to indicate a likelihood ofdeveloping tissue degeneration even after the therapeutic intervention.

The patient may initially give consent to participate in a longitudinalstudy (302) so that the MRI data of the patient may be retained at adatabase accessible for subsequent retrieval when MRI data of thepatient's knee joint at various time points are being compared. In onecursory study, a group of subjects (3 female and 1 male) were recruitedto demonstrate the reproducibility of an example of an MRI scanningprotocol for imaging the knee joint. According to an example of a studyprotocol, subjects were then placed in a wheelchair to have their kneesunloaded for a duration of 30 minutes (304). Thereafter, subjects wereplaced onto stationary base 202 so that the subject's knee joint can besecured in position inside a local coil assembly, as discussed above inassociation with FIG. 2. Subjects were then placed inside the mainmagnet of the MRI scanner for scanning when the knee joint is unloaded(306). Such images may form the baseline images with the knee in anunloaded configuration at 0° flexion angle.

More particularly, the subject's knee joint was secured such that theknee joint was only translatable axially on stationary base 202. Using aratchet to actuate threaded rod 203A, an operator may introduce an axialforce to displace the secured knee joint, resulting in a load that actsacross the lower extremity of the subject. The load may be measured, inreal time, by load cell 206 placed under the orthotic boot 208. As loadcell 206 is MRI compatible, such measurements can be performed in realtime from inside the main magnet of the MRI scanner while the axialforce is being applied or adjusted. In the feasibility study, real-timeforces were visible only to the investigators. Subjects, however, wereasked to remain completely relaxed to avoid active muscle contractionduring scan. The forces were continually recorded throughout.

Notably, the threaded rod with ratchet was adjusted to apply an axialforce (superior/inferior direction) equivalent to 50% body weight of thesubject. Referring to FIG. 3B, the measured axial force initiallyreached 50% body weight (or about 300 N). As the ratchet was released,the measured axial force started to decay. After 2 minutes or so, thedecay was noticeable but not detrimental. As illustrated, the reductionin measured force is less than 100N. The ratchet was adjusted again sothat the measured axial force recovered back to 50% BW, and MRI scanningwas started. In addition to the axial force (superior/inferior), thesecondary forces and moments were also recorded during scan, with anaverage magnitude of 25.6 N and 6.3 N for the anterior/posterior andmedial/lateral forces, and 7.9 Nm, 1 Nm and 5.2 Nm for theflexion/extension, internal/external and varus/valgus moments,respectively.

Returning to FIG. 3A, MRI scanning was initiated as immediate (a) scan(308A) when the measured axial force recovered back to 50% BW. Asexpected, the axial force saw an attenuation during immediate (a) scan.The axial force was again adjusted back to 50% BW at the end ofimmediate (a) and another scan was initiated (308B). The gap frominitial load application (end of 306) to initiation of this scan (308B)was approximately 12 minutes.

The subject was then removed from the scanner and allowed to rest for a15-minute rest period with the imaged knee kept in an unloadedconfiguration (310). Subsequently, the subject was repositioned onstationary base 202 with knees secured for imaging, as discussed abovefor step 308A-308B. Two loaded scans were repeated, defined as immediate(b) scan (312A) and delayed (b) scan (312B), respectively.

For each scan, an example of a three-dimensional spoiled gradientrecalled echo (3D SPGR) with frequency selective fat suppressive imagingcan be performed using the scanning parameters: echo time=3.2 ms,repetition time=15.4 ms, field of view=14 cm, slice thickness=1.5 mm,acquisition matrix=512×512, number of excitations=1, flip angle=20degrees, with resulting voxel dimensions=0.27×0.27×1.5 mm. The scan timecan be 8 minutes. A series of five sequential 3D SPGR series can beacquired to assess bony geometries and cartilage thickness for thefollowing configurations.

In this feasibility study, the ratchet was manually operated and whenthe axial force was measured at 50% of BW, the ratchet was left aloneand the measured axial force started to decay. Yet, this feasibilitystudy demonstrated that the applied load can be largely maintained (<12%reduction on average) throughout the MRI scanning period. Thisfeasibility study further demonstrated that knee position is highlyreproducible (<2° in rotation, <1 mm in translation) across differentscans even though the subject was removed from and then came back tostationary base 202 for subsequent scans. As demonstrated below infurther detail, the feasibility study also demonstrated that themeasurements of cartilage deformation under load are repeatable betweenscans when a pre-load period (˜12 mins) is permitted before starting thescan.

FIG. 3C illustrates an example of workflow 330 for acquiring MRI imagesof the knee joint and subsequent image analysis. Imaging results fromthe feasibility study were acquired and processed in accordance withworkflow 330. After knee joint injury, a patient is subjected to anunloaded and then a loaded MRI scan. These MRI scans generate MRI dataduring a MRI data acquisition process (332). The MRI image data fromthese MRI scans are segmented so that the geometry of the cartilage andthe meniscus are extracted (334). Deformation of the articular cartilageand extrusion of the meniscus are quantified through surfaceregistration (336). Such registration may reveal cartilage contact area338). As a result, a series of outcome metrics to be quantified (340),including, for example, cartilage thickness (340A), cartilage contactarea (340B), meniscal extrusion (340C), and T1ρ or T2 relaxation (340D).The acquisition and analysis process can be repeated at 3, 6 and 12months points (342) so that the knee joint of a subject can belongitudinally monitored over these time points. Such monitoring mayenable assessing the rate of change in, for example, one of the outcomeparameters (340A-340D). Hence, a ‘risk factor’ for long-termdegeneration can be computed.

The standard of care for providing a full diagnosis of joint injury ordegenerative changes is unloaded MRI scanning. However, information canbe gathered about tissue deformation under load in a pre-operatively mayprovide complimentary information for surgical planning. Thisinformation would help the clinician to identify the abnormal jointcontact, and therefore to choose an appropriate surgical technique (useof scaffolds/number of sutures/use of biological augments, amount oftissue resection) to improve the surgical outcomes.

To facilitate access to such information, implementations disclosedherein can provide a platform to evaluate the longitudinal changes inarticular cartilage following joint surgeries (for example, ligamentreconstruction, meniscal repair or transplantation). The ability tolongitudinally track a condition of knee joint is tremendouslybeneficial when the knee joint is subject to a reproducible load hasbeen demonstrated. Such ability is advantageous to aid the understandingof the mechanical pathway to joint degeneration, either with or withoutsurgery. Consider the decision to have surgery after rupture of theanterior cruciate ligament (ACL): for young active patients, surgery ifoften preferable, but for many middle-age to older patients,rehabilitation protocols are used. Implementations disclosed herein mayallow non-operative patients to be followed so as to assess whetherjoint degeneration is progressing, before symptoms emerge.

FIG. 4A shows an example of a segmented MRI knee joint image—acquiredfrom step 332. The MRI image was manually segmented using an imageprocessing tool (e.g., ITK-SNAP) to create 3D models of bone andarticular cartilage. All segmentations were performed by a singleinvestigator. The subchondral bone surface was defined by the sharpcontrast of signal intensity between articular cartilage (bright) andbone (dark) commonly seen in standard imaging protocol. The segmentationrules were defined prospectively: image slices which displayed theanatomy of interest were segmented, except in cases of partial volumeaveraging. The repeatability of image segmentation was assessed byperforming four repeat segmentation trials on the same knee, and thecoefficient of repeatability was determined. The 3-dimensional femurmodels of the loaded configurations were registered to the femur modelof the unloaded configuration using an iterative closest point (ICP)shape matching algorithm.

FIG. 4B shows an example of assessing tibiofemoral position after manualsegmentation of the example MRI knee joint image according to FIG. 4A.The changes in tibiofemoral position were calculated as the tibialmotion in the femoral local coordinate system. The femoral origin wasdefined at the middle point of the medial and lateral epicondyles withthe mediolateral axis (y-axis) pointing medially and the proximal/distalaxis (z-axis) pointing proximally.

FIG. 4C shows an example of a thickness map of the femoral and tibialarticular cartilages after manual segmentation of the example MRI kneejoint image according to FIG. 4A. Cartilage thickness was calculated asthe shortest distance from each point on the subchondral bone surface tothe articular cartilage surface. The cartilage contact region wasdefined as the overlapping contact area of the unloaded tibial andfemoral articular surfaces when aligned to their respective loadedconfiguration. After obtaining the cartilage thickness for all scans,cartilage strain was calculated in the following steps: 1) the surfacemeshes of cartilage from unloaded and loaded configurations were alignedby registering their non-deforming subchondral bone surfaces using theICP algorithm; 2) the original triangular surface meshes were projectedto the transverse plane and resampled to a structured grid (so as tocreate cartilage thickness maps with identical meshes); and 3) cartilagestrain was calculated at each point of the identical meshes. To simplifythe computation, the average strain within the cartilage contact regionwas reported.

The outcome measures included: 1) the percentage reduction of therecorded axial force throughout the scanning, 2) changes in tibiofemoralposition between repeat immediate scans and between repeat delayedscans, and 3) average cartilage strain within the contact region foreach scan. A Mann-Whitney Rank-Sum Test was performed to detectdifferences of cartilage strain between two repeat measurements(immediate (a) vs. immediate (b), and delayed (a) vs. delayed (b)). Thelevel of significance was set at P<0.05.

The average change in tibial position between the repeat scans was: <0.2mm in both the medial/lateral and superior/inferior translation and <0.8mm in anterior/posterior translation; <0.4° in varus/valgus rotation,<1° in internal/external rotation, and <2° in flexion/extension, asillustrated in FIG. 6. The differences in internal/external rotation andanterior/posterior translation between immediate (a) and immediate (b),0.8° and 0.8 mm, respectively, were greater than those between delayed(a) and delayed (b), 0.2° and 0.4 mm. The change in tibial positionbetween scans for individual subjects is listed in Table 1.

TABLE 1 Change in tibiofemoral position between repeat scans at loadedconfiguration. 3 translations (mm) with position sign in anterior,lateral and superior direction, 3 rotations (degree) with positive signin varus, internal and flexion. Subject 1 Subject 2 Subject 3 Subject 4immediate delayed immediate delayed immediate delayed immediate delayed(a) minus (a) minus (a) minus (a) minus (a) minus (a) minus (a) minus(a) minus (b) (b) (b) (b) (b) (b) (b) (b) Rotation VV 0.3 −0.3 −0.2 −0.10.4 0 0.1 (°) IE −2.0 0.6 0.5 0.8 0.2 1.0 0.4 FE 0 −4.0 −3.8 −1.0 −2.40.9 −0.4 Translation ML 0.3 0 −0.2 0 −0.2 0.3 0 (mm) AP 0.3 −1.2 −0.4−1.0 −0.6 0.2 −0.7 SI −0.1 0.1 −0.2 −0.1 −0.3 0 0.2 VV—varus (+)/valgus,IE—internal (+)/external, FE—flexion (+)/extension, ML—medial(+)/lateral, AP—anterior (+)/posterior, SI—superior (+)/inferior (Note:immediate (a) data was not acquired for subject 1)

The coefficient of repeatability (1.96 SD of the differences) of theaverage cartilage thickness within the contact region was 0.078 mm,which represents the minimal detectable change in the cartilagethickness in this study. Compared to the unloaded condition, cartilagethickness decreased within the contact region under load. On average,the tibial articular cartilage within the contact region underwentgreater compressive strain (medial 15.8%, lateral 14.6%) than thefemoral articular cartilage (medial 5.5%, lateral 7.2%). The cartilagestrains of two repeat scans are shown in FIG. 5A-5C. Significantdifferences were found between immediate (a) and immediate (b) in medialfemoral, lateral femoral and lateral tibial cartilages (as shown in FIG.5A); however, no differences were found between delayed (a) and delayed(b) (as shown in FIG. 5B). For contextual information, FIG. 5Cillustrates the weight bearing regions on femur and tibia.

Hence, the feasibility of using a MRI-compatible loading device has beendemonstrated. In particular, some implementations can consistently applya pre-determined load to knee joint during MRI scans. In fact, someimplementations can apply and maintain an axial load (for example, withsmaller than 12% force reduction) to lower limb, while maintaining aconsistent within-subject tibiofemoral position (<1 mm in rotation, and<2° in rotation) during high-resolution MRI scanning. Theseimplementations may allow repeatable tibiofemoral positioning, and thedelayed scan may enable more reproducible measurements of cartilagedeformation in a clinical setting. Such repeatability andreproducibility allow longitudinal studies focused on the progression ofknee joint physiology and pathology including, for example, cartilagethickness, meniscal extrusion, collagen network organization and solidmatrix composition. As demonstrated in further detail below in FIGS.6-10, initial processing of longitudinal MRI data appears to suggestthat cartilage strain of above 28% may be predictive of short termarticular cartilage degeneration.

To identify significant biomarkers for predicting the cartilagedegeneration following meniscal transplantation, a series of outcomebiomarkers of the patients may be evaluated using quantitative MRI,including: cartilage thickness, contact area, meniscal extrusion and T1ρor T2 relaxation times which indicate the structural organization andcomposition of the cartilage solid matrix. Some implementations allow apre-determined load to be reproducibly applied to the knee joint so thatMRI scans can be reproducibly performed to track such outcomebiomarkers. In particular, by acquiring the preoperative andpostoperative quantitative MRI data according to some implementations ofthe disclosure, an empirical model can be developed to predict thelong-term health of articular cartilage following joint injuries or/andsurgeries based on those outcome measures.

Similar to workflow 300 outlined in FIG. 3A, each patient may receivepreoperative MRI scans to assess the outcome biomarker parameters,including baseline cartilage thickness, contact area, meniscal extrusion(if the patient has meniscus) and T1ρ or T2 relaxation times. Next, MRIscans were repeated in a reproducible manner after the patients'surgical treatments to assess the changes in those outcome biomarkers atdifferent follow-ups (See Table 2). The rate of changes from 6 months to18 months estimated by fitting a linear regression model to the outcomebiomarker at different follow-ups will be correlated the outcomes at thefirst follow-up (e.g. 6 months) to determine the early predictors ofcartilage degeneration.

TABLE 2 Predictors of postoperative cartilage degeneration usingquantitative MRI. MRI scans are performed before the surgery and at 6,12 and 18 months (m) after surgery. Pre- operation Follow-ups Rate ofOutcomes (baseline) 6 m 12 m 18 m Changes Cartilage Thickness ✓ ✓ ✓ ✓ 6to 18 m Cartilage Contact Area ✓ ✓ ✓ ✓ 6 to 18 m Meniscal Extrusion ✓ ✓✓ ✓ 6 to 18 m T1ρ and T2 Relaxation ✓ ✓ ✓ ✓ 6 to 18 m Times

Five young patients (2M/3F, age: 21±4 years, weight: 71.8±14.3 kg,height: 1.67±0.04 mm), who were to undergo meniscal allografttransplantation surgery were enrolled following an IRB approved protocolwith informed consent obtained prior to participation. In this study,all patients showed no advanced osteoarthritic findings (<grade II) onknee radiographs, and had undergone prior total meniscectomy.

All subjects underwent imaging of the ipsilateral knee joint prior tosurgery and at their follow-up visits. The preoperative MRI wasperformed within 2 days of the surgery date. The first follow-up MRIswere performed within a time window from 3 to 6 months depending on thecomplexity of surgical procedures.

Examples of MRI images may include coronal high-resolution spoiledgradient echo (SPGR) images (echo time [TE]=3.1 ms, repetition time[TR]=15.5, field of view [FOV]=14 cm, acquisition matrix [AM]=512×512,slice thickness [ST]=1.5 mm, flip angle=20°, receiver bandwidth[RBW]=±41.7 kHz, with pixel dimensions=0.27 mm×0.27 mm), coronal T1ρmapping imaging (TE=2.6 ms, TR=5.0 ms, FOV=15 cm, AM=256×160, ST=3 mm,time of spin lock=0, 20, 40, 60 ms, spin lock frequency=500 Hz,RBW=±41.7 kHz, with pixel dimensions=0.58 mm×0.58 mm), and coronal T2mapping imaging (TE=7.2, 14.4, 21.6, 28.8, 36.0, 43.2, 50.4, 57.6 ms,TR=1000 ms, FOV=14 cm, AM=384×256, ST=3 mm, RBW=±62.5 kHz, with pixeldimensions=0.58 mm×0.58 mm) were acquired using published protocols. Inaddition, a 3D CUBE sequence (TE=31 ms, TR=2500 ms, echo trainlength=40, number of excitations=0.5, ST=0.6 mm, RBW=±41.7 kHz, withpixel dimensions=0.58 mm×0.58 mm) was acquired for meniscalsegmentation.

Consistent with the workflow 300 of FIG. 3A, patients were seated in awheelchair for 30 mins prior to imaging so as to unload the knee beforethe scan. Following the period of unloading, subjects were positionedsupine on top of a MRI-compatible loading device, with the knee in fullextension and no load applied. SPGR, T1ρ, T2 and CUBE images weresequentially acquired. Next, an axial load equal to 50% patient bodyweight was applied at the foot. A second SPGR series (loaded-MRI) wasinitiated after 12 minutes of force application. The delay in imagingwas performed to obtain a more reproducible measurement of cartilagedeformation.

In accordance with workflow 330 from FIG. 3C, the 3D SPGR images weremanually segmented to create 3D model of articular cartilage and bone.Here, cartilage thickness was calculated as the shortest distance fromeach point on the subchondral bone surface to the articular cartilagesurface. Cartilage thickness from both loaded and unloaded conditionswas mapped, as illustrated in FIGS. 6A and 6B. Cartilage deformationunder loaded configuration was assessed as the percentage change inthickness at each point on the subchondral bone surface, as illustratedin FIG. 6C. The region of contact was calculated by cartilage surfaceoverlapping algorithm. For qMRI analysis, the cartilage of the medialand lateral tibial plateaus were manually segmented to define regions ofinterest (ROIs) using custom-developed MATLAB® software (MathWorks,Natick, Mass.) for T2 and T1ρ calculations. ROIs of articular cartilagewere evaluated in consensus by two biomedical engineers with 13 and 6years of qMRI analysis, respectively. Tibial cartilage regions wereautomatically partitioned into two equal laminae: the deep layer andsuperficial layer.

The T1ρ and T2 values within the ROIs were calculated on apixel-by-pixel basis by fitting a mono-exponential decay equation:S(TSL)∝exp(−TSL/T1ρ) and S(TE)∝exp(−TE/T2), respectively. Average T1ρand T2 values within superficial and deep layers were calculated. Next,the 2D T1ρ maps on different slices were overlaid on the 3D anatomicalsurface model of the tibial plateau to create the 3D T1ρ mapping, asillustrated in FIG. 7.

The 3D T2 mapping was created in the same way. To assess spatialvariation in cartilage thickness, T1ρ and T2 times, tibial plateau waspartitioned into two zones (FIG. 6C): 1) Cartilage-Cartilage contact(CC) zone—area not covered by meniscal allograft, and 2)Cartilage-Meniscus contact (CM) zone—area underneath the meniscalallograft at unloaded configuration. The average cartilage thickness,T1ρ and T2 relaxation times in each zone were calculated for eachsubject at pre- and post-operative scans.

First follow-up scans were performed all 5 subjects. The secondfollow-up MRI scans (at 12 months) will be performed in 1 to 3 monthsfor different subjects. Given the procedures of the future follow-up MRIscans are exactly the same, the first follow-up data are used to provethe concepts outlined in this study. A large variability in thecolor-coded map of cartilage deformation on tibial plateau was foundamong the subjects at meniscectomy condition (FIG. 8). The contact areaswere increased by 28% on average (from 155±45 mm2 to 208±79 mm2)following meniscal transplantation. Notable increases of contact areaswere observed, except for one ‘outlier’ patient (patient 3) who had only2% increase.

Follow-up scans were also obtained at 6 months from subject 1-3, at 5months from subject 4, and at 3 months from subject 5. The analysis wasfocused on tibial cartilage of the affected compartment since twosubjects had a concomitant cartilage repair in the femoral condyle.There were minimal differences in average cartilage thickness betweenpreoperative and follow-up scans within both CC and CM zones (Table 3).At follow-up scans, average T1ρ values were notably shorter than theirpreoperative levels within the CM zone (superficial layer: −11%±17%,deep layer: −6%±14%, Table 3). Whereas, changes were less remarkablewithin the CC zone (superficial layer: −3%±17%, deep layer: 0%±14%).However, prolonged T2 values were observed within the CC zone of thedeep layer (8%±23%) at follow-up scans, while such increases were lessremarkable (<3%) within the CM zone or in the superficial layer, asillustrated in FIGS. 9A-9C. Substantial variability was noted in changesamong subjects. Whereas, for the ‘outlier’ patient (patient 3), whoshowed minimal increase in contact area after meniscal transplantation,the T1ρ relaxation times were increased by 11% and 13% within the CMzone of the superficial layer and deep layer, respectively, as shown inFIGS. 10A-10C. No notable changes were seen in the T2 relaxation timesor cartilage thickness for this patient.

TABLE 3 Preoperative and postoperative (follow-up scan) cartilagethickness (Notes: CC—cartilage to cartilage contact zone, CM—cartilageto meniscal allograft contact zone. Thickness values expressed as themean value within each zone.) Preoperative Thickness (mm) PostoperativeThickness (mm) Subject ID CC CM CC CM 1 2.49 1.97 2.52 2.30 2 2.33 2.082.04 1.81 3 3.17 2.59 3.27 2.43 4 2.10 1.93 1.93 1.82 5 2.59 2.48 2.912.66 mean 2.54 2.21 2.53 2.20 change −0.7% −0.2%

Hyaline cartilage is a complex tissue covering the ends of bones at asynovial joint (knee, hip, wrist, shoulder, etc.). It is a biphasic(consisting of fluid and solid components), inhomogeneous andanisotropic tissue that plays a fundamental role in the mechanics of thelow friction, highly loaded joint environment. Chondrocytes, cells incartilage, are remarkably sensitive to their surrounding mechanicalenvironment. For lower extremity joints (e.g. knee) expected tomechanically function for millions of cycles under a range of high loadactivities, it is generally believed that an imbalance between jointmechanics (tissue stress, strain) and the physicochemical ability of thecartilage to adapt to the changes play an important role in the onsetand progression of cartilage degeneration, manifesting asdisorganization of the collagen network, change in solid matrixcomposition, and loss in cartilage thickness or volume.

An individual's response to injury or indeed surgery is highlypatient-specific and can be influenced by many factors: evidence of apre-existing injury, alignment or the joint, genetics, for example.While no single factor can be linked to increased rates of jointdegeneration, it should be possible to quantify ‘risk’ of jointdegeneration in a non-invasive manner. The extent and location ofarticular cartilage deformation under compressive joint loading may bepredictive of predisposition to further cartilage degeneration. Someimplementations may provide the algorithmic aspects to reproduciblyquantify joint tissue deformation under known loads and to followpatients with a metrics sensitive enough to detect early stagedegeneration.

Magnetic resonance imaging (MRI) has been widely used to assess solidmatrix composition and thickness of cartilage in human joints.MRI-compatible loading devices offer the opportunity to explore thisrelationship in patient-based studies by assessing the articularcartilage deformation under controlled joint loads, and by identifyingsequential changes in cartilage solid matrix composition over a periodof time on the same patient. An MRI-compatible loading systems can bedeveloped to assess articular cartilage deformation under static loads.The repeatability of joint positioning between sequential scanningsessions would be advantageous, and the use of the MRI loading systemswithin the larger framework of a clinically useable algorithm would bebeneficial.

Motion may be minimized by reducing image acquisition times, but thiscomes at the expense of increased voxel size (and therefore, decreasedimage resolution) to achieve the same anatomic coverage. To acquire highresolution MRI images of the knee joint, a loading system canadvantageously apply controllable loads with the joint in easilyachieved and repeatable positions across different scans.

One loading system as applied to the knee joint, for example, mayutilize an arrangement of weights connected to a pulley system togenerate a constant force across the lower extremity through a footplate or orthotic. Another loading system may use a spring-likemechanism to apply resistive force when a subject actively pushesagainst a foot pedal during scanning. In an example of a loading system,the ability of patients to maintain a fixed knee position despite theinherent freedom of motion of the foot plate in these designs can bedesirable.

As demonstrated herein, an MRI-compatible, displacement controlled,instrumented system can be developed that is capable of applying knownloads across knee joint while maintaining repeatability inpatient-specific joint orientation between scans conducted at differenttime points. Patient-based data from the disclosure demonstrate thereproducibility of the disclosed MRI-compatible, displacementcontrolled, instrumented system on patients with no recent injury.

As used herein, the terms “comprises” and “comprising” are to beconstrued as being inclusive and open ended, and not exclusive.Specifically, when used in the specification and claims, the terms“comprises” and “comprising” and variations thereof mean the specifiedfeatures, steps or components are included. These terms are not to beinterpreted to exclude the presence of other features, steps orcomponents.

As used herein, the term “exemplary” means “serving as an example,instance, or illustration,” and should not be construed as preferred oradvantageous over other configurations disclosed herein.

As used herein, the terms “about” and “approximately” are meant to covervariations that may exist in the upper and lower limits of the ranges ofvalues, such as variations in properties, parameters, and dimensions. Inone non-limiting example, the terms “about” and “approximately” meanplus or minus 10 percent or less.

Implementations of the subject matter and the functional operationsdescribed in this specification can be implemented in digital electroniccircuitry, in tangibly-implemented computer software or firmware, incomputer hardware, including the structures disclosed in thisspecification and their structural equivalents, or in combinations ofone or more of them. Implementations of the subject matter described inthis specification can be implemented as one or more computer programs,i.e., one or more modules of computer program instructions encoded on atangible non transitory program carrier for execution by, or to controlthe operation of, data processing apparatus. The computer storage mediumcan be a machine-readable storage device, a machine-readable storagesubstrate, a random or serial access memory device, or a combination ofone or more of them.

The term “data processing apparatus” refers to data processing hardwareand encompasses all kinds of apparatus, devices, and machines forprocessing data, including, by way of example, a programmable processor,a computer, or multiple processors or computers. The apparatus can alsobe or further include special purpose logic circuitry, e.g., a centralprocessing unit (CPU), a FPGA (field programmable gate array), or anASIC (application specific integrated circuit). In some implementations,the data processing apparatus and/or special purpose logic circuitry maybe hardware-based and/or software-based. The apparatus can optionallyinclude code that creates an execution environment for computerprograms, e.g., code that constitutes processor firmware, a protocolstack, a database management system, an operating system, or acombination of one or more of them. The present disclosure contemplatesthe use of data processing apparatuses with or without conventionaloperating systems, for example Linux®, UNIX®, Windows®, Mac OS®,Android®, iOS® or any other suitable conventional operating system.

A computer program, which may also be referred to or described as aprogram, software, a software application, a module, a software module,a script, or code, can be written in any form of programming language,including compiled or interpreted languages, or declarative orprocedural languages, and it can be deployed in any form, including as astand-alone program or as a module, component, subroutine, or other unitsuitable for use in a computing environment. A computer program may, butneed not, correspond to a file in a file system. A program can be storedin a portion of a file that holds other programs or data, e.g., one ormore scripts stored in a markup language document, in a single filededicated to the program in question, or in multiple coordinated files,e.g., files that store one or more modules, sub programs, or portions ofcode. A computer program can be deployed to be executed on one computeror on multiple computers that are located at one site or distributedacross multiple sites and interconnected by a communication network.While portions of the programs illustrated in the various figures areshown as individual modules that implement the various features andfunctionality through various objects, methods, or other processes, theprograms may instead include a number of sub-modules, third partyservices, components, libraries, and such, as appropriate. Conversely,the features and functionality of various components can be combinedinto single components as appropriate.

The processes and logic flows described in this specification can beperformed by one or more programmable computers executing one or morecomputer programs to perform functions by operating on input data andgenerating output. The processes and logic flows can also be performedby, and apparatus can also be implemented as, special purpose logiccircuitry, e.g., a central processing unit (CPU), a FPGA (fieldprogrammable gate array), or an ASIC (application specific integratedcircuit).

Computers suitable for the execution of a computer program include, byway of example, can be based on general or special purposemicroprocessors or both, or any other kind of central processing unit.Generally, a central processing unit will receive instructions and datafrom a read only memory or a random access memory or both. The essentialelements of a computer are a central processing unit for performing orexecuting instructions and one or more memory devices for storinginstructions and data. Generally, a computer will also include, or beoperatively coupled to receive data from or transfer data to, or both,one or more mass storage devices for storing data, e.g., magnetic,magneto optical disks, or optical disks. However, a computer need nothave such devices. Moreover, a computer can be embedded in anotherdevice, e.g., a mobile telephone, a personal digital assistant (PDA), amobile audio or video player, a game console, a Global PositioningSystem (GPS) receiver, or a portable storage device, e.g., a universalserial bus (USB) flash drive, to name just a few.

Computer readable media (transitory or non-transitory, as appropriate)suitable for storing computer program instructions and data include allforms of non volatile memory, media and memory devices, including by wayof example semiconductor memory devices, e.g., EPROM, EEPROM, and flashmemory devices; magnetic disks, e.g., internal hard disks or removabledisks; magneto optical disks; and CD ROM and DVD-ROM disks. The memorymay store various objects or data, including caches, classes,frameworks, applications, backup data, jobs, web pages, web pagetemplates, database tables, repositories storing business and/or dynamicinformation, and any other appropriate information including anyparameters, variables, algorithms, instructions, rules, constraints, orreferences thereto. Additionally, the memory may include any otherappropriate data, such as logs, policies, security or access data,reporting files, as well as others. The processor and the memory can besupplemented by, or incorporated in, special purpose logic circuitry.

To provide for interaction with a user, implementations of the subjectmatter described in this specification can be implemented on a computerhaving a display device, e.g., a CRT (cathode ray tube), LCD (liquidcrystal display), or plasma monitor, for displaying information to theuser and a keyboard and a pointing device, e.g., a mouse or a trackball,by which the user can provide input to the computer. Other kinds ofdevices can be used to provide for interaction with a user as well; forexample, feedback provided to the user can be any form of sensoryfeedback, e.g., visual feedback, auditory feedback, or tactile feedback;and input from the user can be received in any form, including acoustic,speech, or tactile input. In addition, a computer can interact with auser by sending documents to and receiving documents from a device thatis used by the user; for example, by sending web pages to a web browseron a user's client device in response to requests received from the webbrowser.

The term “graphical user interface,” or GUI, may be used in the singularor the plural to describe one or more graphical user interfaces and eachof the displays of a particular graphical user interface. Therefore, aGUI may represent any graphical user interface, including but notlimited to, a web browser, a touch screen, or a command line interface(CLI) that processes information and efficiently presents theinformation results to the user. In general, a GUI may include aplurality of user interface (UI) elements, some or all associated with aweb browser, such as interactive fields, pull-down lists, and buttonsoperable by the business suite user. These and other UI elements may berelated to or represent the functions of the web browser.

Implementations of the subject matter described in this specificationcan be implemented in a computing system that includes a back endcomponent, e.g., as a data server, or that includes a middlewarecomponent, e.g., an application server, or that includes a front endcomponent, e.g., a client computer having a graphical user interface ora Web browser through which a user can interact with an implementationof the subject matter described in this specification, or anycombination of one or more such back end, middleware, or front endcomponents. The components of the system can be interconnected by anyform or medium of digital data communication, e.g., a communicationnetwork. Examples of communication networks include a local area network(LAN), a wide area network (WAN), e.g., the Internet, and a wirelesslocal area network (WLAN).

The computing system can include clients and servers. A client andserver are generally remote from each other and typically interactthrough a communication network. The relationship of client and serverarises by virtue of computer programs running on the respectivecomputers and having a client-server relationship to each other.

The specific embodiments described above have been shown by way ofexample, and it should be understood that these embodiments may besusceptible to various modifications and alternative forms. It should befurther understood that the claims are not intended to be limited to theparticular forms disclosed, but rather to cover all modifications,equivalents, and alternatives falling within the spirit and scope ofthis disclosure.

What is claimed is:
 1. A system for securing and loading a knee joint ofa subject for reproducible magnetic resonance imaging (MRI), the systemcomprising: a force sensor assembly adapted to measure a load as appliedon the knee joint of the subject when the force sensor assembly isplaced inside a main magnet of an MRI scanner and remains in directcontact with the subject's lower extremity and wherein the load ismeasured from inside the main magnet of the MRI scanner; a mobile unitcomprising tracks configured to adjust a position of the force sensorassembly attached thereto; a stationary base on which the mobile unitand the force sensor assembly are located, the mobile unit translatablesolely axially on the stationary base such that the knee joint of thesubject, as placed in a straight unbent position over the stationarybase, remains in a fixed location axially and unable to move non-axiallyinside the main magnet of the MRI scanner; and a processor coupled tothe force sensor assembly and programmed to monitor the load beingmeasured by the force sensor assembly throughout an MRI scan of the kneejoint, wherein the processor is in communication with a control unitthat is configured to initiate the MRI scan by operating gradient coilsand a local coil assembly of an MRI scanner when the load has beenapplied to the knee joint for a pre-determined period of time andwherein the load on the knee joint is maintained at a minimum of 40% ofthe subject's body weight throughout the MRI scan such that thesubject's knee joint is reproducibly monitored under the load.
 2. Thesystem of claim 1, wherein the mobile unit is connected to thestationary base by a threaded rod operable to translate the mobile unitsolely axially within the main magnet and along the stationary base. 3.The system of claim 2, wherein the tracks are operable to adjust ananterior/posterior position or a medial/lateral position of the forcesensor assembly.
 4. The system of claim 3, wherein the tracks includevertical tracks operable to adjust the anterior/posterior position ofthe force sensor assembly, and horizontal tracks operable to adjust themedial/lateral position of the force sensor assembly.
 5. The system ofclaim 2, further comprising: a ratchet operable to actuate the threadedrod to displace the knee joint of the subject such that the load isbeing applied to the knee joint that result in a force acting across afoot and an ankle of the subject.
 6. The system of claim 5, wherein theforce sensor assembly comprises: a load cell configured to measure theforce as experienced by the foot and the ankle of the subject; and anorthotic boot configured to support the foot and the ankle of thesubject by holding stationary the foot and the ankle while the forceexperienced by the foot and the ankle is being measured by the loadcell.
 7. The system of claim 1, wherein the stationary base comprises anopening suitable for mounting a local coil assembly; and wherein thesystem further comprises the local coil assembly comprising a base, anaperture on the base, and coils outside of the aperture, wherein theaperture is sized and shaped to fit the knee joint of the subject, andwherein the base is sized and shaped to mate with the opening on thestationary base, wherein the local coil assembly is configured toreceive MRI signals emitted from the knee joint of the subject inresponse to radio frequency (RF) pulses and gradient pulses applied insynchrony, wherein the local coil assembly is further configured totransmit at least one of the RF pulses.
 8. The system of claim 1,further comprising: a shoulder harness attached to the stationary baseand adapted to be wrapped around a shoulder of the subject such that thesubject's shoulder motion is restrained when the knee joint of thesubject is being scanned.
 9. The system of claim 1, further comprising:a waist strap attached to the stationary base and adapted to be wornaround the subject's waist such that the subject's upper body motionsare restrained when the subject's knee joint is being scanned.
 10. Thesystem of claim 1, further comprising: the MRI scanner, comprising: themain magnet configured to generate a volume of magnetic field with fieldinhomogeneity below a defined threshold, the main magnet including abore area sized to accommodate the stationary base on which the subjectis placed to have the knee joint scanned; the gradient coils configuredto generate gradient pulses that provide perturbations to the volume ofmagnetic field such that MRI signals encoding an MRI image according toencoding information from the gradient pulses are emitted from the kneejoint and are subsequently acquired by the local coil assembly mountedon the stationary base; and the control unit in communication with theprocessor and configured to operate: (i) the gradient coils to generatethe gradient pulses and (ii) the local coil assembly to acquire the MRIsignals emitted from the knee joint that encode the MRI image when theload has been applied for a pre-determined period of time.
 11. Thesystem of claim 10, wherein the MRI scanner further comprises aradio-frequency (RF) coil in communication with the control unit andwherein the control unit is further configured to operate the RF coil totransmit RF pulses into the knee joint of the subject.
 12. The system ofclaim 10, further comprising: an analysis computer adapted to quantify,solely by analyzing MRI images of the knee joint, at least one of: acartilage thickness, a cartilage volume, or a cartilage strain, whereinthe analysis computer is adapted to analyze the MRI images of the kneejoint from the same subject but from more than one time point.
 13. Thesystem of claim 12, further comprising an analysis computer adapted todetermine a cartilage strain by comparing a first MRI image from thesubject when the knee joint is unloaded and a second MRI image from thesubject when the load has been applied to the knee joint for thepre-determined period of time.
 14. The system of claim 1, wherein theload is maintained at approximately half the subject's body weight. 15.A method for performing a magnetic resonance imaging (MRI) scan, themethod comprising: placing a knee joint of a subject in a straightunbent position on a stationary base by: securing the knee joint of thesubject into an aperture of a local coil assembly such that the kneejoint of the subject remains in a fixed location axially and unable tomove non-axially inside a main magnet of a MRI scanner while the subjectrests on the stationary base in the straight unbent position throughoutthe MRI scan, the local coil assembly mated with an opening on thestationary base; and configuring a mobile unit that is translatablesolely axially on the stationary base to adjust a position of a forcesensor assembly, wherein the force sensor assembly is configured tomonitor a load as being applied on the knee joint of the subject whenthe force sensor assembly is placed inside the main magnet of the MRIscanner; maintaining the load on the knee joint of the subject while theknee joint of the subject is secured to receive the MRI scan; andinitiating the MRI scan of the knee joint when a pre-determined periodof time has elapsed after application of the load, wherein the load ismaintained at a minimum of 40% of the subject's body weight throughoutthe MRI scan such that the subject's knee is reproducibly monitoredunder the load.
 16. The method of claim 15, wherein maintaining the loadon the knee joint of the subject comprises: using a ratchet system todisplace the knee joint of the subject such that the load is applied tothe knee joint which result in a force acting across a foot and an ankleof the subject, using the force sensor assembly to measure the force asapproximately half the subject's body weight when the subject is placedinside the main magnet for the MRI scan, and using an orthotic boot tosupport the foot and ankle of the subject by holding stationary the footand the ankle while the force experienced by the foot and ankle is beingmonitored.
 17. The method of claim 15, further comprising: sliding thesubject on the stationary base into the main magnet of the MRI scannersuch that the knee joint of the subject is placed into a volume ofmagnetic field generated by the main magnet with field inhomogeneitybelow a defined threshold.
 18. The method of claim 17, furthercomprising: administering an injection of a contrast agent into thesubject to facilitate delineation of the knee joint from an MRI image ofthe subject obtained from the MRI scanner.
 19. The method of claim 15,wherein initiating the MRI scan comprises initiating an imaging sequenceto highlight an MRI characteristic of the knee joint, wherein the MRIcharacteristic includes at least one of: a T2 parameter, a T1 parameter,a T1ρ parameter, a hydrogen density parameter, or a magnetizationtransfer parameter.
 20. The method of claim 15, further comprising:analyzing a first MRI image of the subject obtained at a first timepoint to determine a quantitative biomarker parameter, wherein thequantitative biomarker parameter includes at least one of: a cartilagethickness, a cartilage volume, or a cartilage strain.
 21. The method ofclaim 20, wherein determining the quantitative biomarker parametercomprises: comparing MRI images obtained from the subject when the kneejoint is unloaded and MRI images obtained from the subject when the loadis applied to and maintained at the knee joint.
 22. The method of claim20, further comprising: analyzing a second MRI image of the subjectobtained at a second time point to determine the quantitative biomarkerparameter, and determining a rate of change for the quantitativebiomarker parameter by comparing the quantitative biomarker parameterdetermined at the first time point with the quantitative biomarkerparameter determined at the second time point.